Morphogenesis is characterized by the specialization of cells which, in response to various signals, coordinate growth, movement, and interactions such that these events give rise to a functional organism. One of the major problems in developmental biology is to identify those signals and determine their mechanism(s) of action. Many models attribute an inherent role to the cell surface, either invoking specific cohesion molecules or modifications of more general components, but limited progress has been made in identifying these structures. The ultimate goal of this research is to understand how specific cell-cell contact formation can influence the spacial and temporal organization of a metazoan. To approach this goal, we will undertake a study of a surface protein involved in cell cohesion in a model system, D. discoideum. The protein was identified by the ability of a monoclonal antibody to inhibit cell-cell contact formation at a specific developmental stage. We are now in a position to characterize the protein and the possible modifications which may affect its expression and function. Part of such studies involves purifying the protein to raise polyclonal sera and a panel of monoclonals directed against different moieties of the protein. Such sera will be invaluable in studies of the regulation of the protein at transcriptional and post-transcriptional levels as well as in disecting the mechanism(s) by which it functions to affect selective cell cohesion. For these and future studies involving, e.g., site-directed mutagenesis, a most valuable tool will be that provided by the mutants to be isolated which are defective in the protein. Continued investigations will lead to examining if this cohesion molecule also plays a role in the spacial and temporal organization of the developing organism.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034561-02
Application #
3285812
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1985-09-05
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
Pauly, P C; Klein, C (1996) An uncleaved glycosylphosphatidylinositol signal mediates Ca(2+)-sensitive protein degradation. Biochem J 317 ( Pt 2):533-40
Pauly, P C; Klein, C (1995) Lack of glycosyl-phosphatidylinositol anchoring leads to precursor retention by a unique mechanism in Dictyostelium discoideum. Biochem J 306 ( Pt 3):643-50
Souza, G M; Klein, C; Maia, J C et al. (1994) Calcium uptake and gp80 messenger RNA destabilization follows cAMP receptor down regulation in Dictyostelium discoideum. Cell Signal 6:883-95
da Silva, A M; Klein, C (1991) Biochemical and functional characterization of a glycolipid anchored cell adhesion molecule in Dictyostelium discoideum. Cell Biol Int Rep 15:1065-82
Juliani, M H; Souza, G M; Klein, C (1990) cAMP stimulation of Dictyostelium discoideum destabilizes the mRNA for 117 antigen. J Biol Chem 265:9077-82
da Silva, A M; Klein, C (1990) Cell adhesion in transformed D. discoideum cells: expression of gp80 and its biochemical characterization. Dev Biol 140:139-48
da Silva, A M; Klein, C (1990) A rapid posttranslational myristylation of a 68-kD protein in D. discoideum. J Cell Biol 111:401-7
da Silva, A M; Klein, C (1989) Characterization of a glycosyl-phosphatidylinositol degrading activity in Dictyostelium discoideum membranes. Exp Cell Res 185:464-72
Browne, L H; Sadeghi, H; Blumberg, D et al. (1989) Re-expression of 117 antigen, a cell surface glycoprotein of aggregating cells, during terminal differentiation of Dictyostelium discoideum prespore cells. Development 105:657-64
Kraft, B; Chandrasekhar, A; Rotman, M et al. (1989) Dictyostelium erasure mutant HI4 abnormally retains development-specific mRNAs during dedifferentiation. Dev Biol 136:363-71

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